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Low burden of minimal residual disease prior to transplantation in children with very high risk acute lymphoblastic leukaemia: The NOPHO ALL2008 experience
Copenhagen Univ Hosp, Rigshosp, Dept Paediat & Adolescent Med, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Lund Univ, Lund, Sweden.
Rigshosp, Copenhagen Univ Hosp, Dept Clin Immunol, Tissue Typing Lab, Copenhagen, Denmark.
Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp & Clintec, Stockholm, Sweden.
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2019 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 184, no 6, p. 982-993Article in journal (Refereed) Published
Abstract [en]

The population-based Nordic/Baltic acute lymphoblastic leukaemia (ALL) Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol combined minimal residual disease (MRD)-driven treatment stratification with very intense first line chemotherapy for patients with high risk ALL. Patients with MRD >= 5% at end of induction or >= 10(-3) at end of consolidation or following two high risk blocks were eligible for haematopoietic cell transplantation (HCT) in first remission. After at least three high risk blocks a total of 71 children received HCT, of which 46 had MRD >= 5% at end of induction. Ten patients stratified to HCT were not transplanted; 12 received HCT without protocol indication. Among 69 patients with evaluable pre-HCT MRD results, 22 were MRD-positive, one with MRD >= 10(-3). After a median follow-up of 5 center dot 5 years, the cumulative incidence of relapse was 23 center dot 5% (95% confidence interval [CI]: 10 center dot 5-47 center dot 7) for MRD-positive versus 5 center dot 1% (95% CI: 1 center dot 3-19 center dot 2), P = 0 center dot 02) for MRD-negative patients. MRD was the only variable significantly associated with relapse (hazard ratio 9 center dot 1, 95% CI: 1 center dot 6-51 center dot 0, P = 0 center dot 012). Non-relapse mortality did not differ between the two groups, resulting in disease-free survival of 85 center dot 6% (95% CI: 75 center dot 4-97 center dot 2) and 67 center dot 4% (95% CI: 50 center dot 2-90 center dot 5), respectively. In conclusion, NOPHO block treatment efficiently reduced residual leukaemia which, combined with modern transplant procedures, provided high survival rates, also among pre-HCT MRD-positive patients.

Place, publisher, year, edition, pages
2019. Vol. 184, no 6, p. 982-993
Keywords [en]
acute lymphoblastic leukaemia, haematopoietic stem cell transplantation, minimal residual disease, children
National Category
Hematology Pediatrics
Identifiers
URN: urn:nbn:se:uu:diva-379930DOI: 10.1111/bjh.15761ISI: 000460183700012PubMedID: 30680711OAI: oai:DiVA.org:uu-379930DiVA, id: diva2:1299674
Available from: 2019-03-28 Created: 2019-03-28 Last updated: 2019-03-28Bibliographically approved

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Arvidson, Johan

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